Possible relation of hemin-induced HO-1 expression to the upregulation of VEGF and BDNF mRNA levels in rat C6 glioma cells.
Glial cells are generally considered to contribute to retaining the integrity of neural function through the protection of neuronal cells against neurodegenerative insults and also expected to play a potential role in the protection of cerebrovascular systems from various toxic insults of hemorrhaged blood, thus proposing a possible implication of glial cells in the recovery of brain function from the damage caused by cerebral hemorrhage. Based on this hypothetical idea, the direct effect of hemin on the expression of genes encoding heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) in glial cells was examined using rat C6 glioma cells as an in vitro model system. Hemin elevated both HO-1 and VEGF mRNA levels in the glioma cells at the concentration causing no critical damage to the cells, and the elevation of BDNF mRNA levels was also observed by exposing the cells to hemin under the same conditions. Furthermore, the elevation of VEGF and BDNF mRNA levels induced by hemin was blocked by pretreatment of the cells with the agents inhibiting not only HO-1 gene expression but also its enzymatic activity. These pharmacological studies indicate that hemin can induce the enhancement of VEGF and BDNF gene expression probably through the mechanism mediated by HO-1 activity in the glioma cells, proposing the possibility that glial cells are capable of contributing to the recovery of brain function from the damage caused by cerebral hemorrhage through the production of neurogenic and angiogenic factors.
Morita
Kyoji
K
Laboratory of Neuropharmacology, Department of Nursing, Shikoku University School of Health Sciences, Ohjin, Tokushima, 771-1192, Japan. kmorita@shikoku-u.ac.jp
Lee
Mi-Sook
MS
Her
Song
S
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006427:Hemin / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D006427:Hemin; D051547:Heme Oxygenase-1